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Alessandro Deplano     Other 
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Alessandro Deplano published an article in January 2019.
Top co-authors
Valentina Onnis

141 shared publications

A Department of Life and Environmental Sciences - Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences , University of Cagliari , Cagliari , Italy

Jan Balzarini

78 shared publications

KU Leuven—University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven B-3000, Belgium;(S.L.);(J.B.)

Sandra Liekens

33 shared publications

KU Leuven—University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven B-3000, Belgium;(S.L.);(J.B.)

Salvatore Pacifico

26 shared publications

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy

Monica Demurtas

7 shared publications

Dipartimento di Scienze della Vita e dell’Ambiente, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato (Cagliari), Italy

16
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35
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Publication Record
Distribution of Articles published per year 
(2014 - 2019)
Total number of journals
published in
 
12
 
Publications See all
Article 0 Reads 0 Citations Benzylamides and piperazinoarylamides of ibuprofen as fatty acid amide hydrolase inhibitors Alessandro Deplano, Mariateresa Cipriano, Federica Moraca, E... Published: 27 January 2019
Journal of Enzyme Inhibition and Medicinal Chemistry, doi: 10.1080/14756366.2018.1532418
DOI See at publisher website
Article 0 Reads 0 Citations Benzylamides and piperazinoarylamides of ibuprofen as fatty acid amide hydrolase inhibitors Alessandro Deplano, Mariateresa Cipriano, Federica Moraca, E... Published: 27 January 2019
Journal of Enzyme Inhibition and Medicinal Chemistry,
PubMed View at PubMed ABS Show/hide abstract
Fatty Acid Amide Hydrolase (FAAH) is a serine hydrolase that plays a key role in controlling endogenous levels of endocannabinoids. FAAH inhibition is considered a powerful approach to enhance the endocannabinoid signalling, and therefore it has been largely studied as a potential target for the treatment of neurological disorders such as anxiety or depression, or of inflammatory processes. We present two novel series of amide derivatives of ibuprofen designed as analogues of our reference FAAH inhibitor Ibu-AM5 to further explore its structure-activity relationships. In the new amides, the 2-methylpyridine moiety of Ibu-AM5 was substituted by benzylamino and piperazinoaryl moieties. The obtained benzylamides and piperazinoarylamides showed FAAH inhibition ranging from the low to high micromolar potency. The binding of the new amides in the active site of FAAH, estimated using the induced fit protocol, indicated arylpiperazinoamides binding the ACB channel and the cytosolic port, and benzylamides binding the ACB channel.
Article 0 Reads 1 Citation Development and Validation of Molecular Overlays Derived from Three-Dimensional Hydrophobic Similarity with PharmScreen Javier Vázquez, Alessandro Deplano, Albert Herrero, Tiziana ... Published: 16 July 2018
Journal of Chemical Information and Modeling, doi: 10.1021/acs.jcim.8b00216
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Article 0 Reads 3 Citations Novel propanamides as fatty acid amide hydrolase inhibitors Alessandro Deplano, Carmine Marco Morgillo, Monica Demurtas,... Published: 01 August 2017
European Journal of Medicinal Chemistry, doi: 10.1016/j.ejmech.2017.05.033
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Article 0 Reads 3 Citations Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 rev... Angela Corona, Valentina Onnis, Alessandro Deplano, Giulia B... Published: 10 July 2017
Pathogens and Disease, doi: 10.1093/femspd/ftx078
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In the continuous effort to identify new HIV-1 inhibitors endowed with innovative mechanisms, the dual inhibition of different viral functions would provide a significant advantage against drug-resistant variants. The HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) is the only viral-encoded enzymatic activity that still lacks an efficient inhibitor. We synthesized a library of 3,5-diamino-N-aryl-1H-pyrazole-4-carbothioamide and 4-amino-5-benzoyl-N-phenyl-2-(substituted-amino)-1H-pyrrole-3-carbothioamide derivatives and tested them against RNase H activity. We identified the pyrazolecarbothioamide derivative A15, able to inhibit viral replication and both RNase H and RNA-dependent DNA polymerase (RDDP) RT-associated activities in the low micromolar range. Docking simulations hypothesized its binding to two RT pockets. Site-directed mutagenesis experiments showed that, with respect to wt RT, V108A substitution strongly reduced A15 IC50 values (12.6-fold for RNase H inhibition and 4.7-fold for RDDP), while substitution A502F caused a 9.0-fold increase in its IC50 value for RNase H, not affecting the RDDP inhibition, reinforcing the hypothesis of a dual-site inhibition. Moreover, A15 retained good inhibition potency against three non-nucleoside RT inhibitor (NNRTI)-resistant enzymes, confirming a mode of action unrelated to NNRTIs and suggesting its potential as a lead compound for development of new HIV-1 RT dual inhibitors active against drug-resistant viruses.
Article 0 Reads 3 Citations Homology modeling of a Class A GPCR in the inactive conformation: A quantitative analysis of the correlation between mod... Stefano Costanzi, Matthew Skorski, Alessandro Deplano, Brett... Published: 01 November 2016
Journal of Molecular Graphics and Modelling, doi: 10.1016/j.jmgm.2016.10.004
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
With the present work we quantitatively studied the modellability of the inactive state of Class A G protein-coupled receptors (GPCRs). Specifically, we constructed models of one of the Class A GPCRs for which structures solved in the inactive state are available, namely the β2 AR, using as templates each of the other class members for which structures solved in the inactive state are also available. Our results showed a detectable linear correlation between model accuracy and model/template sequence identity. This suggests that the likely accuracy of the homology models that can be built for a given receptor can be generally forecasted on the basis of the available templates. We also probed whether sequence alignments that allow for the presence of gaps within the transmembrane domains to account for structural irregularities afford better models than the classical alignment procedures that do not allow for the presence of gaps within such domains. As our results indicated, although the overall differences are very subtle, the inclusion of internal gaps within the transmembrane domains has a noticeable a beneficial effect on the local structural accuracy of the domain in question.
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